The proposed research will (1) define the action of volatile anesthetics (halothane, enflurane and diethyl ether) on the cyclic 3',5'-adenosine monophosphate (cAMP) system of myocardium and (2) clarify the mechanisms by which these anesthetics act on the enzymes of the cAMP system: adenylate cyclase, cAMP-phosphodiesterase, and protein kinase. The changes in adenylate cyclase responsiveness caused by anesthetics and the interaction of anesthetics with several transmitters controlling cardiovascular functions will be determined. This study will establish whether, and to what extent, the effects of these anesthetics on the heart, mainly cardiac depression and the sensitization of the conductive system of the heart to catecholamines, are related to the effects of these anesthetics on the cAMP system in the heart. Rat, cat, guinea pig, and dog heart and cat right ventricular papilllry muscle and isolated perfused heart will be used for in vitro biochemical and functional studies, respectively. The effect of halothane, enflurance, and diethyl ether at increasing concentrations on adenylate cyclase and cAMP-phosphodiesterase will be determined in tissue homogenates by the methods of Krishna and Thompson-Appleman, respectively. Cyclic AMP in intact tissues will be measured according to Gilman. Protein content will be measured by the procedure of Lowry.